ABSTRACT
The retinoids comprise a structurally diverse series of compounds that possess pharmacologic activities generally attributable to the naturally occurring congeners, retinol and retinoic acid. The toxicologic activities of the synthetic retinoids are similar to those of their natural congeners as well. This chapter reviews briefly the dysmorphogenicity induced by prenatal retinoid exposure in animals and humans and summarizes the concepts put forward to explain the morphogenetic basis of these malformations. It compares structure-activity relationships from in vitro and in vivo techniques to assess the therapeutic and chemopreventive properties and the potential developmental toxicities of the retinoids. The goal of the present communication is to point out those features of the retinoid skeleton associated with improved therapeutic ratios. The placental permeability of retinol, its esters, and its binding protein has been studied. Retinoids apparently act as diffusible morphogens capable of altering embryonic cell migration, proliferation, and differentiation, functioning in control of normal as well as abnormal embryogenesis.
